Reuters Health Information (2012-12-06): Early response points to boceprevir combo success in HCV
Drug & Device Development
Early response points to boceprevir combo success in HCV
Last Updated: 2012-12-06 16:58:16 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Patients with advanced fibrosis/cirrhosis from hepatitis C virus (HCV), genotype-1 will sometimes have a sustained virologic response (SVR) to peginterferon-ribavirin plus boceprevir - and early results can point to responders, researchers say.
Dr. Savino Bruno told Reuters Health by email that "the majority... of patients with cirrhosis (F4 Metavir histologic score), the most difficult to treat subset of HCV-infected ones, may be efficaciously cured by triple therapy with boceprevir."
And it seems the lead-in phase response can help predict patients' risk:benefit ratio, Dr. Bruno of A. O. Fatebenefratelli e Oftalmico, Milan, Italy, and colleagues decided after reviewing data from two randomized trials.
The trials originally included 1,500 patients. The new study, reported online November 28 in the Journal of Hepatology, included 178 patients with a Metavir score of F3 or F4. The patients, previously untreated or treatment failures, all received a four-week lead-in of peginterferon/ribavirin. Following that, they all continued on peginterferon/ribavirin for another 44 weeks, adding either placebo, boceprevir using response-guided therapy, or boceprevir given directly.
In the response guided group, the duration of therapy was based on a prespecified decision point whereby those with undetectable HCV-RNA at week eight were eligible for shorter therapy.
In the placebo group, no one with a lower than 1-log10 decline in HCV-RNA at the end of the lead-in phase went on to an SVR. However, in both of the boceprevir groups, the SVR rates for similar patients were 11% to 33% in the F3 patients and 10% to 14% in those rated F4.
In the boceprevir patients with high baseline viral load (greater than 2 X 106 IU/mL) the overall SVR rate was only 6%.
The authors say the study provides "important new information regarding predictors of SVR in this patient population."
SVR rates in patients with advanced fibrosis/cirrhosis with a 1-log10 decline or greater in HCV RNA after the four-week lead-in were 77-87% after completion of 44 weeks of triple therapy, compared with 50% for 48 weeks of peginterferon/ribavirin alone.
Among those with undetectable HCV RNA at week eight (corresponding to four weeks of triple therapy), SVR rates were 79-80% in the boceprevir response guided group and 90-93% in the direct group. The investigators conclude, therefore, that "early viral kinetics can be used to predict the response to treatment in patients with cirrhosis."
It appears that the longer treatment with four weeks of peginterferon/ribavirin plus 44 weeks of boceprevir provides the greatest benefits. Also, the investigators say, "The degree of HCV-RNA log decline after a four-week lead-in provides important information for determining whether the benefits of initiating first generation protease inhibitor therapy outweigh the risks for each individual patient."
The study was funded by Merck, developers of the protease inhibitor boceprevir. Dr. Bruno has relationships with Merck and other companies as do a number of the authors. Six are current or former employees of a subsidiary of Merck.
J Hepatol 2012.